A KCNB1 gain of function variant causes developmental delay and speech apraxia but not seizures.

ABSTRACT: Objective: Numerous pathogenic variants in KCNB1, which encodes the voltage-gated potassium channel, K_V2.1, are linked to developmental and epileptic encephalopathies and associated with loss-of-function, -regulation, and -expression of the channel. Here we describe a novel de novo variant (P17T) occurring in the K_V2.1 channel that is associated with a gain-of-function (GoF), with altered steady-state inactivation and reduced sensitivity to the selective toxin, guanxitoxin-1E and is clinically associated with neurodevelopmental disorders, without seizures. Methods: The autosomal dominant variant was identified using whole exome sequencing (WES). The functional effects of the KCNB1 variant on the encoded K_V2.1 channel were

SUBMITTER: Veale EL 

PROVIDER: S-EPMC9810754 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature